Abstract
There is growing evidence that cardiovascular health can be affected by exposure to methylmercury (MeHg), by a mechanism involving oxidative stress. Paraoxonase 1 (PON1) is a high-density lipoprotein-bound enzyme that hydrolyzes toxic oxidized lipids and protects against cardiovascular diseases. Evidence from in vitro studies indicates that MeHg can inhibit PON1 activity but little is known regarding this effect in humans. We investigated whether increased blood mercury levels are associated with decreased serum PON1 activity in Cree people who are exposed to MeHg by fish consumption. We conducted a multi-community study of 881 Cree adults living in Eastern James Bay communities (Canada). Multivariate analyses considered sociodemographic, anthropometric, clinical, dietary and lifestyle variables and six PON1 gene variants (rs705379 (−108C/T), rs662 (Q192R), rs854560 (L55M), rs854572 (−909C/G), rs854571 (−832C/T) and rs705381 (−162C/T)). In a multiple regression model adjusted for all potential confounding factors and the rs854560 PON1 variant, a statistically significant MeHg*rs705379 interaction was observed. Blood mercury levels were inversely associated with serum PON1 activities in individual homozygous for the −108T allele (P=0.009). Our results suggest a gene–environment interaction between the rs705379 polymorphism and MeHg exposure on PON1 activity levels in this aboriginal population. This finding will need to be replicated in other population studies.
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Acknowledgements
This scientific communication is a report from the Nituuchischaayihtitaau Aschii Multi-Community Environment-and-Health Longitudinal Study in Iiyiyiu Ashii supported by the Cree people of Northern Quebec, the Cree First Nations and the Cree Board of Health and Social Services of James Bay through financial contributions from Niskamoon Corporation. We gratefully acknowledge the support of the Natural Sciences and Engineering Research Council of Canada’s Metals in the Human Environment Strategic Network. A complete list of sponsors is available at http://www.ncbi.nlm.nih.gov/pubmed/20077280. We also acknowledge the support of FRQS Environmental Health Research Network.
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Drescher, O., Dewailly, E., Diorio, C. et al. Methylmercury exposure, PON1 gene variants and serum paraoxonase activity in Eastern James Bay Cree adults. J Expo Sci Environ Epidemiol 24, 608–614 (2014). https://doi.org/10.1038/jes.2013.96
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DOI: https://doi.org/10.1038/jes.2013.96